Dissolution of amyloid fibrils by flavonoids and other compounds

• US 9,463,195 B2
• Filed: 12/14/2007
• Issued: 10/11/2016
• Est. Priority Date: 12/15/2006
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Eisenberg, David S., Balbirnie, Melinda
• Primary Examiner(s): Anderson, James D
• Application Number:
  US12/519,058
• Publication Number:
  US 20100048510A1
• Time in Patent Office: 3,224 Days
• Field of Search: 514/82
• US Class Current: 1/1
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61M 1/30 Single needle dialysis ; Reciprocating systems, alternately withdrawing blood from and returning it to the patient, e.g. single-lumen-needle dialysis or single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Methods for disrupting amyloid fibrils in a subject, comprising combining an effective amount of a β-2 microglobulin fibril disrupting compound with a medium associated with the subject, are disclosed. The invention also relates to combining the β-2 microglobulin fibril disrupting compound ex vivo with the blood during dialysis treatment of an animal. It also relates to methods for determining which compounds are effective at disrupting amyloid fibrils in a medium.

Claims

1. A dialysis system comprising an upstream blood side, an artificial kidney, and a downstream blood side, and benserazide hydrochloride, stictic acid, haemmatommic acid, meclocycline sulfosalicylate, dobutamine hydrochloride, apomorphine hydrochloride or primaquine diphosphate.

2. The dialysis system of claim 1, wherein the system comprises benserazide hydrochloride.

3. The dialysis system of claim 1, wherein the system comprises stictic acid.

4. The dialysis system of claim 1, wherein the system comprises haemmatommic acid.

5. The dialysis system of claim 1, wherein the system comprises meclocycline sulfosalicylate.

6. The dialysis system of claim 1, wherein the system comprises dobutamine hydrochloride.

7. The dialysis system of claim 1, wherein the system comprises apomorphine hydrochloride.

8. The dialysis system of claim 1, wherein the system comprises primaquine diphosphate.

9. A method for treating dialysis-related amyloidosis in a subject comprising combining blood of the subject with a β

-2 microglobulin fibril disrupting compound selected from the group consisting of one or more of benserazide hydrochloride, stictic acid, haemmatommic acid, meclocycline sulfosalicylate, dobutamine hydrochloride, apomorphine hydrochloride, and primaquine diphosphate, wherein the β

-2 microglobulin fibril disrupting compound is combined ex vivo with the blood during dialysis treatment of the subject.

10. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises benserazide hydrochloride.

11. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises stictic acid.

12. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises haemmatommic acid.

13. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises meclocycline sulfosalicylate.

14. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises dobutamine hydrochloride.

15. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises apomorphine hydrochloride.

16. The method of claim 9, wherein the β

-2 microglobulin fibril disrupting compound comprises primaquine diphosphate.